DESCRIPTION: (Applicant's Description) Ovarian carcinoma represents the fourth leading cause of cancer death in the female population and is the most fatal gynecologic malignancy. Secondary to its presentation as advanced disease in the majority of cases and its low prevalence, strategies that center on therapeutics or screening are unlikely to impact the overall death rate. Therefore, when considering strategies to decrease the deaths attributable to ovarian carcinoma, prevention of disease represents the most rational approach. This approach to intervention is consistent with statements from the National Cancer Institute, which have identified a need for develop ment of primary and secondary chemoprevention strategies in ovarian carcinoma. Many human cancers are now recognized to be the result of accumu lated genetic lesions, which culminate in the transformed malignant phenotype. Carcinogenesis can then be considered an aberrance of differentiation. This pathology of differentiation offers a defined target for pharmacological intervention. To this end, recent investigations of retinoids and progesterone derivatives have demonstrated their efficacy as differentiating agents in neoplastic and normal ovarian epithelial cells. These studies, therefore, now offer a biologic rationale for exploring chemoprevention in the context of ovarian carcinoma. Moreover, the populations of patients who have undergone frontline therapy and undergo second look laparotomy where no residual disease is detected represent an ideal population to study secondary chemoprevention. Therefore, the purpose of our proposed studies is to develop chemopreventive strategies and validate potential surrogate endpoint bio-markers in women at high risk for ovarian carcinoma. As such, these studies will address an important and underdeveloped investigational endeavor in women's health. Clearly, chemoprevention represents the most rational investigational strategy to achieve a meaningful reduction in deaths from ovarian carcinoma. More importantly, identification of models that would simulate a high-risk population with validated bio-markers would significantly impact the underexploited strategy of cancer chemoprevention for ovarian carcinoma and lead to subsequent endeavors in this neglected area of study.